PROJECT SUMMARY BACKGROUND. PrEP has dramatically changed the promise of HIV prevention, particularly for transgender women (TGW) who are among the highest risk group for HIV in the U.S. While PrEP reduces HIV acquisition by >90% with adequate adherence, TGW face multiple transgender-specific barriers with PrEP access, uptake, adherence, and retention. The PIs have longstanding partnerships with community-based organizations that provide gender-affirming services to this group in Providence, RI and operate one of the first clinical PrEP programs in the U.S., led by our team at Miriam Hospital/Brown University. CONCEPTUAL MODEL. The intervention package (?PrEP N? Shine?) is based on over a decade of formative and programmatic work grounded in the social-cognitive and contextual realities of high-risk TGW, and as such, the conceptual model underlying the intervention draws on Empowerment Theory and Social Cognitive Theory. The ?PrEP N? Shine? package includes two separate but complementary interventions: 1) peer-led, strengths-based case management (SBCM) for PrEP linkage and uptake; and 2) a resource-efficient, adaptive ?stepped-care? technology and counseling intervention to optimize PrEP adherence. ?Stepped-care? is a healthcare delivery model in which the least resource intensive part of an intervention is delivered first, and only those who continue to have problems adhering to PrEP receive the more resource-intensive components. APPROACH. Initially, we will continue to work with community members and a community advisory board to further inform the ?PrEP N? Shine? intervention (Aim 1a). Next, we will iteratively refine the intervention, in an open pilot trial with exit interviews, with up to 10 TGW to enhance participant acceptability, feasibility of study procedures, and finalize study protocols (Aim 1b). For Aim 2, we will conduct a pilot randomized controlled trial (RCT) of the ?PrEP N? Shine? intervention using a 2-stage randomization design: For Stage 1, we aim randomize 106 TGW who are candidates for PrEP to receive either the peer-led SBCM for PrEP linkage and uptake or standard of care (SOC; i.e., PrEP referrals only). For Stage 2, those from Stage 1 who initiate PrEP (n~44), regardless of their randomization condition, will then be equally re-randomized to either the resource-efficient, adaptive ?stepped-care? intervention to optimize PrEP adherence (initially TGW in this arm will receive daily 2-way gender-affirming text message reminders, and then those continuing to have poor adherence will receive the 4 more intensive counseling sessions) or the SOC condition. Primary outcomes include PrEP linkage and uptake; PrEP adherence (both biomedical and self-report assessments); and retention in PrEP care. INNOVATION. The ?PrEP N? Shine? intervention is highly scalable and sustainable in the real world, as it takes into account the ?future of PrEP access,? while simultaneously 1) addressing the barriers surrounding access, 2) aiding in navigating linkage, and for those who need it, both insurance and free PrEP program options, and 3) reducing barriers to, and building skills to support, PrEP adherence (once TGW have access to PrEP).